2016
Phase I study of pemetrexed with sorafenib in advanced solid tumors
Poklepovic A, Gordon S, Shafer DA, Roberts JD, Bose P, Geyer CE, McGuire WP, Tombes MB, Shrader E, Strickler K, Quigley M, Wan W, Kmieciak M, Massey HD, Booth L, Moran RG, Dent P. Phase I study of pemetrexed with sorafenib in advanced solid tumors. Oncotarget 2016, 7: 42625-42638. PMID: 27213589, PMCID: PMC5173162, DOI: 10.18632/oncotarget.9434.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCohort StudiesFemaleHumansInflammationMaleMaximum Tolerated DoseMiddle AgedNeoplasmsNiacinamidePemetrexedPhenylurea CompoundsPTEN PhosphohydrolaseSorafenibTreatment OutcomeTriple Negative Breast NeoplasmsConceptsAdvanced solid tumorsDay 1Solid tumorsOral sorafenibDose scheduleBreast cancerTriple-negative breast cancerDose-escalation schemaPhase II dosePhase I trialSorafenib dosingSorafenib therapyStable diseaseCohort BComplete responseI trialPartial responseTolerable combinationRadiographic assessmentCumulative toxicityCombination treatmentPatientsSorafenibPhase IAntitumor activityA phase I study of indoximod in patients with advanced malignancies
Soliman HH, Minton SE, Han HS, Ismail-Khan R, Neuger A, Khambati F, Noyes D, Lush R, Chiappori AA, Roberts JD, Link C, Vahanian NN, Mautino M, Streicher H, Sullivan DM, Antonia SJ. A phase I study of indoximod in patients with advanced malignancies. Oncotarget 2016, 7: 22928-22938. PMID: 27008709, PMCID: PMC5008412, DOI: 10.18632/oncotarget.8216.Peer-Reviewed Original ResearchConceptsStable diseaseDose levelsC-reactive protein levelsReactive protein levelsAdvanced solid tumorsTumor-mediated immunosuppressionPhase I trialUntreated brain metastasesMetastatic solid malignanciesMultiple dose levelsAntigen autoantibodiesBrain metastasesCheckpoint inhibitorsImmune correlatesPrimary endpointSecondary endpointsAdvanced malignanciesCRP levelsI trialOral inhibitorAutoimmune diseasesMarrow functionSolid malignanciesInclusion criteriaExclusion criteria
2014
Phase I Trial of Bortezomib (PS-341; NSC 681239) and “Nonhybrid” (Bolus) Infusion Schedule of Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory Indolent B-cell Neoplasms
Holkova B, Kmieciak M, Perkins EB, Bose P, Baz RC, Roodman GD, Stuart RK, Ramakrishnan V, Wan W, Peer CJ, Dawson J, Kang L, Honeycutt C, Tombes MB, Shrader E, Weir-Wiggins C, Wellons M, Sankala H, Hogan KT, Colevas AD, Doyle LA, Figg WD, Coppola D, Roberts JD, Sullivan D, Grant S. Phase I Trial of Bortezomib (PS-341; NSC 681239) and “Nonhybrid” (Bolus) Infusion Schedule of Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory Indolent B-cell Neoplasms. Clinical Cancer Research 2014, 20: 5652-5662. PMID: 25248382, PMCID: PMC4233160, DOI: 10.1158/1078-0432.ccr-14-0805.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityCombination of bortezomibCommon hematologic toxicityCommon nonhematologic toxicitiesIndolent B-cell neoplasmsRefractory multiple myelomaDose-escalation designNon-Hodgkin lymphomaTotal response rateB-cell malignanciesB-cell neoplasmsPharmacodynamic study resultsNonhematologic toxicitySchedule regimenStable diseaseComplete remissionHematologic toxicityPartial remissionClinical responseInvestigator's discretionDosing regimenI trialPharmacokinetic findingsSensory neuropathyInfusion schedule
2013
A Phase I Trial of Vorinostat and Alvocidib in Patients with Relapsed, Refractory, or Poor Prognosis Acute Leukemia, or Refractory Anemia with Excess Blasts-2
Holkova B, Supko JG, Ames MM, Reid JM, Shapiro GI, Perkins EB, Ramakrishnan V, Tombes MB, Honeycutt C, McGovern RM, Kmieciak M, Shrader E, Wellons MD, Sankala H, Doyle A, Wright J, Roberts JD, Grant S. A Phase I Trial of Vorinostat and Alvocidib in Patients with Relapsed, Refractory, or Poor Prognosis Acute Leukemia, or Refractory Anemia with Excess Blasts-2. Clinical Cancer Research 2013, 19: 1873-1883. PMID: 23515411, PMCID: PMC3618599, DOI: 10.1158/1078-0432.ccr-12-2926.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAdultAgedAnemia, Refractory, with Excess of BlastsAntineoplastic Combined Chemotherapy ProtocolsCell Line, TumorCyclin-Dependent Kinase Inhibitor p21FemaleFlavonoidsHumansHydroxamic AcidsLeukemiaMaleMaximum Tolerated DoseMiddle AgedMyeloid Cell Leukemia Sequence 1 ProteinPiperidinesPrognosisProto-Oncogene Proteins c-bcl-2RecurrenceRNA Polymerase IITreatment OutcomeVorinostatYoung AdultConceptsMaximum-tolerated dosePoor-prognosis acute leukemiaExcess blasts-2Objective responseQT prolongationAcute leukemiaBlasts-2Phase I trialBone marrow responseCardiac arrhythmia atrial fibrillationArrhythmia atrial fibrillationEvaluable patientsStable diseaseVorinostat pharmacokineticsDisease stabilizationMaintenance infusionI trialMarrow responsePharmacodynamic effectsRefractory anemiaIntravenous infusionLoading infusionPatientsVorinostatSecondary objectivePhase I trial of bortezomib and dacarbazine in melanoma and soft tissue sarcoma
Poklepovic A, Youseffian L, Winning M, Birdsell CA, Crosby NA, Ramakrishnan V, Ernstoff MS, Roberts JD. Phase I trial of bortezomib and dacarbazine in melanoma and soft tissue sarcoma. Investigational New Drugs 2013, 31: 937-942. PMID: 23315028, PMCID: PMC3844155, DOI: 10.1007/s10637-012-9913-8.Peer-Reviewed Original ResearchConceptsSoft tissue sarcomasPhase I trialTissue sarcomasPartial responseI trialPhase II dosesDurable complete responseAmine precursor uptakeTwenty-eight patientsProteasome inhibitor bortezomibHuman melanoma cell linesMurine xenograft tumor modelXenograft tumor modelCKIT mutationsDecarboxylation (APUD) tumorsProphylactic antiemeticsRECIST v1.0Eight patientsComplete responseMelanoma cell linesWeekly dosesDose escalationAgent dacarbazinePreclinical studiesDose levels
2012
Phase I Trial of Belinostat and Bortezomib in Patients with Relapsed or Refractory Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia in Blast Crisis - One Year Update
Holkova B, Bose P, Tombes M, Shrader E, Wan W, Weir-Wiggins C, Stoddert E, Sankala H, Kmieciak M, Roberts J, Garcia-Manero G, Grant S. Phase I Trial of Belinostat and Bortezomib in Patients with Relapsed or Refractory Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia in Blast Crisis - One Year Update. Blood 2012, 120: 3588. DOI: 10.1182/blood.v120.21.3588.3588.Peer-Reviewed Original ResearchHematopoietic stem cell transplantationStem cell transplantationAcute myeloid leukemiaRefractory acute leukemiaDose level 5Myelodysplastic syndromeStable diseaseCycles of treatmentPartial responseComplete responseAcute leukemiaChronic myelogenous leukemiaCML-BCAdverse eventsI trialMyelogenous leukemiaDay 1Allogeneic hematopoietic stem cell transplantationIncomplete blood count recoveryTreatment-related adverse eventsPrimary acute myeloid leukemiaAcute leukemia refractoryBlood count recoveryDose level 4Second partial responsePhase I Trial of Bortezomib (PS-341; NSC 681239) and Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory Indolent B-Cell Neoplasms - Update of the “Bolus” Infusion Schedule of Alvocidib.
Holkova B, Perkins E, Bose P, Sullivan D, Baz R, Tombes M, Shrader E, Ramakrishnan V, Wan W, Sankala H, Kmieciak M, Roberts J, Grant S. Phase I Trial of Bortezomib (PS-341; NSC 681239) and Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory Indolent B-Cell Neoplasms - Update of the “Bolus” Infusion Schedule of Alvocidib. Blood 2012, 120: 2959. DOI: 10.1182/blood.v120.21.2959.2959.Peer-Reviewed Original ResearchAdverse eventsInfusion scheduleMultiple myelomaI trialDose levelsAbsolute neutrophil count decreaseGrade 2 adverse eventsCTCAE version 4Grade 5 eventsIndolent B-cell neoplasmsNeutrophil count decreasePrior systemic therapyPhase II studyECOG performance scoreRefractory multiple myelomaTreatment of recurrentTumor lysis syndromePhase I trialSchedule of administrationCombination of bortezomibIndolent B-cellExpression of pJNKB-cell neoplasmsNF-κB DNA bindingMcl-1
2011
Phase I Trial of Belinostat and Bortezomib in Patients with Relapsed or Refractory Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia in Blast Crisis
Holkova B, Tombes M, Shrader E, Cooke S, Wan W, Sankala H, Kmieciak M, Roberts J, Garcia-Manero G, Grant S. Phase I Trial of Belinostat and Bortezomib in Patients with Relapsed or Refractory Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia in Blast Crisis. Blood 2011, 118: 2598. DOI: 10.1182/blood.v118.21.2598.2598.Peer-Reviewed Original ResearchRefractory acute leukemiaMyelodysplastic syndromeAcute leukemiaChronic myelogenous leukemiaMyelogenous leukemiaI trialCML-BCBlast crisisDay 1ECOG performance score 0Hematopoietic stem cell transplantationPerformance score 0Phase II dosesRecent preclinical findingsPeripheral sensory neuropathySerious adverse eventsMinute intravenous infusionPhase I trialPhase II evaluationPrimary acute myelogenous leukemiaSchedule of administrationStem cell transplantationBiphenotypic acute leukemiaCombination of bortezomibAcute myelogenous leukemiaPhase I Trial of Bortezomib (PS-341; NSC 681239) and Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory B-Cell Neoplasms
Holkova B, Perkins EB, Ramakrishnan V, Tombes MB, Shrader E, Talreja N, Wellons MD, Hogan KT, Roodman GD, Coppola D, Kang L, Dawson J, Stuart RK, Peer C, Figg WD, Kolla S, Doyle A, Wright J, Sullivan DM, Roberts JD, Grant S. Phase I Trial of Bortezomib (PS-341; NSC 681239) and Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory B-Cell Neoplasms. Clinical Cancer Research 2011, 17: 3388-3397. PMID: 21447728, PMCID: PMC3096752, DOI: 10.1158/1078-0432.ccr-10-2876.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityCombination of bortezomibFebrile neutropeniaPharmacodynamic studiesDay 1Refractory B-cell neoplasmsElevated aspartate aminotransferase levelsCommon hematologic toxicityCommon nonhematologic toxicitiesPhase II studyRefractory multiple myelomaPhase I studiesAspartate aminotransferase levelsB-cell malignanciesB-cell neoplasmsHematologic toxicityIntravenous pushNonhematologic toxicityStable diseaseAminotransferase levelsI trialII studyPartial responseComplete responseDose escalation
2008
Phase I Trial of Bortezomib (NSC 681239) and Flavopiridol (NSC 649890) in Patients with Recurrent or Refractory Indolent B-Cell Neoplasms.
Grant S, Sullivan D, Roodman D, Stuart R, Perkins E, Kolla S, Ramakrishnan V, Wright J, Colevas A, Tombes M, Roberts J. Phase I Trial of Bortezomib (NSC 681239) and Flavopiridol (NSC 649890) in Patients with Recurrent or Refractory Indolent B-Cell Neoplasms. Blood 2008, 112: 1573. DOI: 10.1182/blood.v112.11.1573.1573.Peer-Reviewed Original ResearchB-cell neoplasmsDose levelsBolus scheduleI trialMinor responseNF-kappaB nuclear localizationIndolent B-cell neoplasmsPhase II evaluationPhase I trialPhospho-JNKCorrelative laboratory studiesNF-kappaB DNA bindingChronic lymphocytic leukemiaB-cell malignanciesBone marrow CD138Mcl-1Evaluable patientsStable diseaseEligible patientsPostural hypotensionHerpes zosterPartial responseRefractory diseaseStandard therapySystemic therapyPhase I Trial of Vorinostat (SAHA) in Combination with Alvocidib (Flavopiridol) in Patients with Relapsed, Refractory or (Selected) Poor Prognosis Acute Leukemia or Refractory Anemia with Excess Blasts-2 (RAEB-2)
Grant S, Kolla S, Sirulnik L, Shapiro G, Supko J, Cooper B, Perkins E, Ramakrishnan V, Espinoza-Delgado I, Tombes M, Roberts J. Phase I Trial of Vorinostat (SAHA) in Combination with Alvocidib (Flavopiridol) in Patients with Relapsed, Refractory or (Selected) Poor Prognosis Acute Leukemia or Refractory Anemia with Excess Blasts-2 (RAEB-2). Blood 2008, 112: 2986. DOI: 10.1182/blood.v112.11.2986.2986.Peer-Reviewed Original ResearchAcute leukemiaDose levelsStandard therapyI trialDay 1Grade 4 non-hematologic toxicityPoor-prognosis acute leukemiaDe novo acute leukemiaExcess blasts-2High-risk AMLNon-hematologic toxicitiesRemission induction failurePoor risk factorsImatinib-Refractory Chronic Myeloid LeukemiaPhase I trialPhase II evaluationAML/MDSCorrelative laboratory studiesNovo acute leukemiaChronic myeloid leukemiaHDAC inhibitor vorinostatCDK inhibitor flavopiridolAbsence of leukemiaPost-treatment effectsBolus schedule
2005
Phase I Trial of Bortezomib (NSC 681239) and Flavopiridol (NSC 649890) in Patients with Recurrent or Refractory Indolent B-Cell Neoplasms.
Grant S, Sullivan D, Roodman D, Stuart R, Perkins E, Ramakrishnan V, Wright J, Colevas A, Roberts J. Phase I Trial of Bortezomib (NSC 681239) and Flavopiridol (NSC 649890) in Patients with Recurrent or Refractory Indolent B-Cell Neoplasms. Blood 2005, 106: 3338. DOI: 10.1182/blood.v106.11.3338.3338.Peer-Reviewed Original ResearchI trialDose levelsPre-existing peripheral neuropathyIndolent B-cell lymphomaNF-kappaB nuclear localizationIndolent B-cell neoplasmsCase of exacerbationPhase I trialPhase II evaluationPhospho-JNKCorrelative laboratory studiesNF-kappaB DNA bindingB-cell lymphomaB-cell malignanciesBone marrow CD138B-cell neoplasmsMcl-1Eligible patientsStable diseaseHerpes zosterPartial responseRefractory diseaseStandard therapySystemic therapyComplete response
2002
Phase I trial and correlative laboratory studies of bryostatin 1 (NSC 339555) and high-dose 1-B-D-arabinofuranosylcytosine in patients with refractory acute leukemia.
Cragg LH, Andreeff M, Feldman E, Roberts J, Murgo A, Winning M, Tombes MB, Roboz G, Kramer L, Grant S. Phase I trial and correlative laboratory studies of bryostatin 1 (NSC 339555) and high-dose 1-B-D-arabinofuranosylcytosine in patients with refractory acute leukemia. Clinical Cancer Research 2002, 8: 2123-33. PMID: 12114412.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityPhase I trialComplete remissionCorrelative laboratory studiesI trialAcute leukemiaSplit courseContinuous infusionVivo administrationBryostatin 1Ara-C dose levelsAutologous bone marrow transplantationMajor dose-limiting toxicityEx vivoRefractory acute leukemiaUnfavorable prognostic characteristicsHigh-risk featuresLeukemia-free survivalBone marrow transplantationCourse of therapyPKC activityTransfusion requirementsRefractory leukemiaRefractory/Latter patients
1999
Leucovorin, 5-fluorouracil, and gemcitabine: A phase I study
Poplin E, Roberts J, Tombs M, Grant S, Rubin E. Leucovorin, 5-fluorouracil, and gemcitabine: A phase I study. Investigational New Drugs 1999, 17: 57-61. PMID: 10555123, DOI: 10.1023/a:1006239200772.Peer-Reviewed Original ResearchConceptsCombination of leucovorinECOG performance status 0Refractory solid tumor malignanciesMedian performance statusPerformance status 0Phase I trialSolid tumor malignanciesTreatment of lungPrior chemotherapyPrior therapyStatus 0Performance statusStarting doseHepatic reserveI trialPartial responseMedian ageGemcitabine administrationDisease progressionDrug sequenceBreast cancerChemotherapy agentsMedian numberLeucovorinDay 28
1987
Phase I trial of tiazofurin administered by i.v. bolus daily for 5 days, with pharmacokinetic evaluation.
Roberts JD, Stewart JA, McCormack JJ, Krakoff IR, Culham CA, Hartshorn JN, Newman RA, Haugh LD, Young JA. Phase I trial of tiazofurin administered by i.v. bolus daily for 5 days, with pharmacokinetic evaluation. Journal Of The National Cancer Institute 1987, 71: 141-9. PMID: 3802111.Peer-Reviewed Original ResearchConceptsTreatment interruptionTransient toxic effectsM2/dayTreatment coursePhase I clinical trialToxic effectsAntitumor activityPhase II trialPhase I trialBolus IV infusionFrequent treatment interruptionsSerum biochemical abnormalitiesSystemic toxic effectsCoadministration of allopurinolMurine tumor modelsUric acid productionLow dose levelsSignificant antitumor activityBolus dailyInjury manifestTransient pericarditisII trialSerum hemoglobinI trialIV infusion